An exploration of how to define and measure the evolution of behavior, learning, memory and mind across the full phylogenetic tree of life.

There are probably few terms in evolutionary studies regarding neuroscience issues that are used more frequently than 'behavior', 'learning', 'memory', and 'mind'. Yet there are probably as many different meanings of these terms as there are users of them. Further, investigators in such studies, while recognizing the full phylogenetic spectrum of life and the evolution of these phenomena, rarely go beyond mammals and other vertebrates in their investigations; invertebrates are sometimes included. What is rarely taken into consideration, though, is that to fully understand the evolution and significance for survival of these phenomena across phylogeny, it is essential that they be measured and compared in the same units of measurement across the full phylogenetic spectrum from aneural bacteria and protozoa to humans. This paper explores how these terms are generally used as well as how they might be operationally defined and measured to facilitate uniform examination and comparisons across the full phylogenetic spectrum of life. This paper has 2 goals: (1) to provide models for measuring the evolution of 'behavior' and its changes across the full phylogenetic spectrum, and (2) to explain why 'mind phenomena' cannot be measured scientifically at the present time.

A behavioral homeostasis theory of habituation and sensitization: II. Further developments and predictions.

Habituation may be viewed as a decremental behavioral change to iterative stimuli of little immediate relevance. It is observed from protozoa to humans, indicating its evolutionary significance. If habituation is interpreted as the process of filtering out unimportant repetitive stimuli, then how should sensitization be interpreted? The 'behavioral homeostasis theory' of these two behaviors is based on the notion that organisms at a high level of 'alertness' prior to experiencing a new iterative stimulus will show a large initial response followed by a decrement (habituation) if the stimulus is of little significance. Conversely, the same organism at a low level of 'alertness' will show a small initial response to the same stimulus followed by an increase in 'alertness' and a larger response to the next stimulus (sensitization) in order to receive enough information to assess its significance. Circadian rhythmicity is hypothesized to play a role in determining 'alertness' to a new iterative stimulus at any given time. The level of responsiveness in initial habituaters and sensitizers, as an asymptote is approached, is a balance between being too 'alert' to an unimportant stimulus and missing other significant stimuli, and being too 'un-alert' and missing a change in the relevance of the present iterative stimulus. The concept of 'behavioral homeostasis' includes behaviors beyond habituation and sensitization across phylogeny. It includes instinctive as well as learned, and group as well as individual behavior. Such behavioral homeostatic processes to optimize detection and assessment of constantly occurring external stimuli are critical for organism survival. Clinical implications of this theory are also examined.

Cost-effectiveness of single-dose methotrexate compared with laparoscopic treatment of ectopic pregnancy.

OBJECTIVE: To evaluate the cost-effectiveness of treatment with intramuscular (IM) methotrexate compared with fallopian tube-sparing laparoscopy for small unruptured ectopic pregnancy. METHODS: A decision-analytic model accounting for varying resolution rates, complication rates, and cost estimates was built to compare the use of methotrexate with laparoscopy. Meta-analysis results of studies identified by a MEDLINE search for IM methotrexate resolution rates and tube-sparing laparoscopy resolution rates were used in model estimation. A similar process was used to generate model complication rates. Data on associated resource use were derived from established clinical guidelines. Estimates of 1998 costs incurred by provider organizations were calculated using data from a large managed care organization. RESULTS: The average methotrexate resolution rate among the studies included was 87% (range 75-90%). The average laparoscopy resolution rate was 91% (range 72-100%). Complication rates for methotrexate ranged from 0% to 22%, with an average of 10% for minor complications, and from 0% to 11% for serious complications, with an average of 7%. Complication rates for laparoscopy ranged from 0% to 8% for intraoperative complications, with an average of 2%, and from 0% to 15% for postoperative complications, with an average of 9%. Baseline model estimates indicated an average cost saving of more than $3000 per resolved ectopic pregnancy with methotrexate treatment compared with laparoscopy. Results of extensive sensitivity analyses supported the finding of a cost saving with methotrexate treatment. CONCLUSION: Single-dose methotrexate is a cost-saving, nonsurgical, fallopian tube-sparing treatment for ectopic pregnancy.

Torg osteolysis syndrome.

We describe a 9-year-old girl who initially presented at age 4 with evidence of arthritis in her hands, feet, and large joints. Although she had a partial response to anti-inflammatory medications and had some laboratory results consistent with inflammatory disease, radiographs showed carpal and tarsal osteolysis associated with interphalangeal joint erosions. There was also widening of the shafts of the metacarpals and metatarsals with thinning of the cortices. Based on both the clinical progression of her illness and the radiologic characteristics, this child most likely has the Torg syndrome.

Correlations between change in disease activity and changes in peripheral blood lymphocyte subsets in patients with juvenile dermatomyositis.

OBJECTIVE: To investigate whether changes in peripheral blood lymphocytes correlate with changes in disease activity in juvenile dermatomyositis (JDM). METHODS: Clinical changes in disease expression measured by a disease activity score were correlated with changes in percentages of peripheral blood lymphocyte subsets. RESULTS: Changes in the percentage of peripheral blood CD19 positive lymphocytes (B cells) correlated with changes in disease activity (Spearman rank coefficients = 0.47, p = 0.02). There were no significant correlations in disease activity with changes of T cell subsets or the T cell activation markers CD25 or DR. CONCLUSION: Change in the percentage of peripheral blood B cells correlates with change in disease activity in patients with JDM. This variable may be of use as an indicator of immunologic activity and response to therapy.

Habituation of the galvanic skin response to tone as a function of age.

Habituation of the galvanic skin response (GSR) to tone in male college students varying in age from 18-39 years old was examined. Older subjects habituated more slowly to tone than did younger ones. This confirmed our past work on habituation of the GSR to electric shock. The GSR is shown to be a sensitive and reliable measure of small differences in age as it affects learning. The clinical usefulness of this quantitative and sensitive measure in detecting small and early changes in learning and memory deficits associated with age and dementia is discussed.

Initial habituation or sensitization of the GSR depends on magnitude of first response.

Habituation and sensitization of the galvanic skin response (GSR) to shock were studied in college males. One would expect that at any given time individuals vary on a continuum in the degree of their initial GSR responsiveness to a stimulus. Here it is shown that those on the higher end of the continuum are more likely to show a response decrement between trials 1 and 2 when this stimulus is presented intermittently (i.e., habituate), while subjects at the lower end of the continuum are more likely to show a response increment between trials 1 and 2 (i.e., sensitize) to the same intermittent stimulus. Following these initial and opposite changes on the first two trials, which bring all subjects to approximately the same level of responsiveness, they all now behave similarly and continue to show habituation. Previous work on subhuman species showed that habituation and sensitization curves had certain characteristic similarities across species. The present work shows that some of these similarities also occur in humans. One may speculate, that as with other characteristics that are similar across species, they have survival value.

Habituation of the galvanic skin response in adult males as a function of age.

Habituation of the galvanic skin response (GSR) to electric shock was studied in 28 male college students, 18-39 years old. A 60-Hz shock of 244.0-msec duration was presented every 1-3 min above the right ankle in a preprogrammed sequence. The GSR, measured as a change in palmar skin conductance to the shock, was examined over the first 17 shock trials. The habituation curve showed the typical large decrement over the first few trials followed by a smaller one over several more trials. The initial rate of habituation (percent decrement between shock trials 1 and 3) was shown to be age related even though none of the subjects would be considered old (18-39 years old). The younger the subject, the faster the initial habituation or, conversely, the older the subject the slower the rate (rs = -.50, N = 28, p less than 0.005). The asymptote did not vary with age. That such dramatic changes occur in the CNS of young males over a relatively few years is not unknown. PET studies of the caudate nucleus in normal males showed an exponential decrease in dopamine receptors with about half of the decrease occurring rapidly between the ages of 20 and 30 (Wagner, H.N., Jr. Diag. Imaging Nov.: 138-145; 1985). The usefulness of the GSR in detecting age effects in other kinds of learning, such as Pavlovian conditioning, is being explored, as well as its usefulness in detecting early learning/memory loss in aging and the dementias.

Experimental murine invasive pulmonary aspergillosis.

A new model of invasive pulmonary aspergillosis (IPA) was developed in immunosuppressed mice. Intranasal route of inoculation was used to deliver predictable numbers of Aspergillus flavus conidia. The LD50 was determined to be 2.7 X 10(2) viable conidia, and a combination of quantitative culture and determination of chitin content was shown to best measure the progression of pulmonary disease. The evolution of IPA in these mice conformed with what has been reported in human cases of aspergillosis; both histopathology of the pulmonary lesions and dissemination pattern resembled their human counterparts. The authors hope to use this model to study virulence mechanisms of Aspergillus and novel therapeutic methods.

Silicone rubber applied within the eye: a preliminary study.

Clear, room temperature vulcanizing silicone rubber (RTV) has already been shown to have well-defined optical and mechanical properties that allow its use as an active optical element. In this work RTV is considered as a possible material for substitution of damaged and/or diseased parts of the human eye, such as the cornea and crystalline lens. The interaction of cured and uncured RTV with eye tissue and eyelike tissue was investigated, and the results support the use of this material in the eye.

Anticonvulsant drug antagonism of delta9tetrahydrocannabinol-induced seizures in rabbits.

A population of New Zealand White rabbits exhibit behavioral convulsions when given low doses of psychoactive cannabinoids of marijuana. Carbamazepine, diazepam and phenytoin were most effective in blocking these convulsions caused by delta9tetrahydrocannabinol (delta9THC). Phenobarbital and ethosuximide also blocked convulsions but only at toxic doses. Cannabidiol was effective in blocking convulsions when given concurrently with, but not prior to delta9THC.